Polymeric multilayer film for use in bioprocessing applications

Abstract

The presently disclosed subject matter is directed to a polymeric, multilayer film suitable for use in a variety of applications, including (but not limited to) the manufacture of bioprocessing containers. The disclosed film comprises a sealant layer comprising: (i) one or more ethylene/alpha olefin copolymers with an average density lower than 0.922 g/cc; (ii) one or more polymers with an average density higher than or equal to 0.950 g/cc and selected among ethylene/alpha olefin copolymers and/or ethylene homopolymers; (iii) high molecular weight siloxane polymers; optionally, at least one gas barrier layer and an outer skin layer. The sealant layer of the disclosed films provides for a low blocking effect and for high seal strength. In addition, the surface of the sealant layer is inert and substantially free from migratory surface additives and from metal containing particulate additives, such that, when the film is used for manufacturing bioprocessing containers, cell growth and products harvesting are not affected. A method for manufacturing the film, a bioprocessing container comprising the film and a method for culturing cells in such container are also herein disclosed.

1 . A polymeric, multilayer film comprising:
 a sealant layer comprising:   (i) 58-95.5 wt % in respect of the total weight of the sealant layer of one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc;   (ii) 4-10 wt % in respect of the total weight of the sealant layer of one or more polymers having an average density higher than or equal to 0.950 g/cc and selected among one or more ethylene/alpha olefin copolymers and/or one or more ethylene homopolymers;   (iii) 0.5-2.0 wt % in respect of the total weight of the sealant layer of high molecular weight siloxane polymers;
 an outer skin layer comprising one or more polymers selected from the group consisting of: (co)polyesters, polyamides; high-density polyethylene (HDPE), polypropylene (PP) and their admixtures. 
   
     
     
         2 . The polymeric, multilayer film of  claim 1  wherein the one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc are selected from the group consisting of linear low density polyethylene (LLDPE), very low density polyethylene (VLDPE), ultra low density polyethylene (ULDPE) and mixtures thereof. 
     
     
         3 . The polymeric, multilayer film of  claim 1  wherein the one or more polymers having an average density higher than or equal to 0.950 g/cc is high density polyethylene (HDPE) or mixtures thereof. 
     
     
         4 . The polymeric, multilayer film of  claim 1  comprising 75-95.5 wt % in respect of the total weight of the sealant layer of one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc. 
     
     
         5 . The polymeric, multilayer film of  claim 1  comprising:
 (i) 75-93.5 wt % in respect of the total weight of the sealant layer of one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc; 
 (ii) 6-10 wt % in respect of the total weight of the sealant layer of one or more polymers having an average density higher than or equal to 0.950 g/cc and selected among one or more ethylene/alpha olefin copolymers and/or one or more ethylene homopolymers; 
 (iii) 0.5 to 1.2 wt % in respect of the total weight of the sealant layer of high molecular weight siloxane polymers. 
 
     
     
         6 . The polymeric, multilayer film of  claim 1  comprising:
 (i) 75-95.2 wt % in respect of the total weight of the sealant layer of one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc; 
 (ii) 4-6 wt % in respect of the total weight of the sealant layer of one or more polymers having an average density higher than or equal to 0.950 g/cc and selected among one or more ethylene/alpha olefin copolymers and/or one or more ethylene homopolymers; and 
 (iii) 0.8 to 2.0 wt % in respect of the total weight of the sealant layer of high molecular weight siloxane polymers. 
 
     
     
         7 . The polymeric, multilayer film of claim wherein each one of the at least one gas barrier layer(s), if present, independently comprises a major proportion of one or more polymers selected from the group consisting of poly(glycolic acid) (PGA), polyamides, ethylene vinyl alcohol (EVOH) and mixtures thereof. 
     
     
         8 . The polymeric, multilayer film of  claim 1  wherein the outer skin layer comprises a major proportion of one or more polymers selected from the group consisting of (co)polyesters, polyamides, high-density polyethylene (HDPE), polypropylene (PP) and their admixtures. 
     
     
         9 . The polymeric, multilayer film of  claim 8  wherein the outer skin layer comprises a major proportion of one or more polymers selected from the group consisting of: (co)polyesters, polyamides, and their admixtures. 
     
     
         10 . The polymeric, multilayer film of  claim 1  further comprising:
 one or more bulk layer independently comprising one or more polymers selected from the group consisting of low density polyethylene (LDPE), ethylene-vinyl acetate copolymers (EVA), linear low density polyethylenes (LLDPE), linear very low density polyethylenes (VLDPE), ethylene/acrylic acid copolymers (EAA), ethylene/methacrylic acid copolymers (EMAA), ethylene/methyl acrylate copolymers (EMA), ethylene/butyl acrylate copolymers (EBA), ionomers, and mixtures thereof; 
 
       and/or
 one or more tie layer independently comprising one or more polymers selected from the group consisting of ethylene-unsaturated acid copolymers, ethylene-unsaturated ester copolymers, polyurethane, ethylene-vinyl acetate copolymers, ethylene-(meth)acrylic acid copolymers, ethylene/methyl acrylate copolymers, ethylene homo-polymers or co-polymers modified with anhydride or carboxylic acid functionalities, mixtures thereof and mixtures of any of these resins with an ethylene homo- or co-polymer, anhydride modified grafted linear low density polyethylene, anhydride grafted low density polyethylene, homogeneous ethylene/alpha-olefin copolymer, anhydride grafted ethylene/vinyl acetate copolymer, anhydride grafted ethylene/methyl acrylate copolymers, anhydride grafted styrene/ethylene/butadiene/styrene copolymers. 
 
     
     
         11 . The polymeric, multilayer film of  claim 1  having a thickness comprised between 30 and 600 microns. 
     
     
         12 . The polymeric, multilayer film of  claim 1  wherein the film comprises migratory surface additives and from metal containing particulate additives in a total amount of 0.05 wt % or less, based on the total weight of the film. 
     
     
         13 . A method for manufacturing the film of  claim 1  comprising a step of extruding all the layers of the film, or at least some layers thereof, comprising the sealant layer, through a round die. 
     
     
         14 . A flexible bioprocessing container comprising at least a polymeric, multilayer film comprising:
 a sealant layer comprising:   (i) 58-95.5 wt % in respect of the total weight of the sealant layer of one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc;   (ii) 4-10 wt % in respect of the total weight of the sealant layer of one or more polymers having an average density higher than or equal to 0.950 g/cc and selected among one or more ethylene/alpha olefin copolymers and/or one or more ethylene homopolymers;   (iii) 0.5-2.0 wt % in respect of the total weight of the sealant layer of high molecular weight siloxane polymers;   an outer skin layer comprising one or more polymers selected from the group consisting of: (co)polyesters, polyamides; high-density polyethylene (HDPE), polypropylene (PP) and their admixtures,
 wherein said film is sealed to define an interior compartment of the container and wherein the sealant layer of said film forms an inner surface of the container. 
   
     
     
         15 . The flexible bioprocessing container of  claim 14 , wherein the container is pre-sterilized. 
     
     
         16 . A method for culturing cells comprising either the steps of:
 (i) providing a flexible bioprocessing container;   (ii) introducing a liquid medium into the interior compartment of the container;   (iii) inoculating the liquid medium with cells, and   (iv) incubating the cells within the interior compartment of the container under suitable conditions for cell growth;   or the steps of:   (i) providing a flexible bioprocessing container;   (ii) pre-inoculating a liquid medium with cells;   (iii) introducing the pre-inoculated liquid medium into the interior compartment of the container, and   (iv) incubating the cells within the interior compartment of the container under suitable conditions for cell growth;   in either instance, the flexible bioprocessing container comprising at least a polymeric, multilayer film comprising:
 a sealant layer comprising: 
   (i) 58-95.5 wt % in respect of the total weight of the sealant layer of one or more ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc;   (ii) 4-10 wt % in respect of the total weight of the sealant layer of one or more polymers having an average density higher than or equal to 0.950 g/cc and selected among one or more ethylene/alpha olefin copolymers and/or one or more ethylene homopolymers;   (iii) 0.5-2.0 wt % in respect of the total weight of the sealant layer of high molecular weight siloxane polymers;   an outer skin layer comprising one or more polymers selected from the group consisting of: (co)polyesters, polyamides; high-density polyethylene (HDPE), polypropylene (PP) and their admixtures.   
     
     
         17 . The polymeric, multilayer film of  claim 1  wherein the sealant layer further comprises (iv) 5-30 wt % in respect of the total weight of the sealant layer of elastomeric cyclic olefin copolymers (COC) with glass transition temperature (Tg) lower than 20° C., wherein the glass transition temperature is measured by differential scanning calorimetry (DSC) according to ASTM D-3418. 
     
     
         18 . The polymeric, multilayer film of  claim 1  wherein the at least one gas barrier layer comprises one or more polymers selected from the group consisting of poly(glycolic acid) (PGA), polyamides, ethylene vinyl alcohol (EVOH) and mixtures thereof. 
     
     
         19 . The polymeric, multilayer film of  claim 5  wherein the ethylene/alpha olefin copolymers having an average density lower than 0.922 g/cc are selected among LLDPE, VLDPE, ULDPE and mixtures thereof, and/or the one or more polymers having an average density higher than or equal to 0.950 g/cc is HDPE or mixtures thereof. 
     
     
         20 . The polymeric, multilayer film of  claim 9  wherein the one or more polymers selected from the group consisting of: (co)polyesters, polyamides, and their admixtures of the outer skin layer is polybutylene terephthalate (PBT) and copolymers thereof, and wherein such PBT copolymer is a copolymer of terephthalic acid, butylene glycol and a further glycol (PBTG).